(Applicant's Abstract): A major complication of CF is prolonged lung inflammation in response to infections. Agents produced during infections exacerbate the underlying defect in cystic fibrosis, inadequate fluid secretion. The investigators hypothesize that two of these exacerbating agents, EGF and TGFalpha act through a PI-3 kinase-signaling pathway leading to phosphatidylinositol 3,4,5 trisphosphate (PIP3) production that triggers translocation of the protein kinase C isoform, PKC epsilon, from the cytosol to the membrane where it phosphorylates relevant substrates (i.e. ion channels). They will test whether other cellular responses contributing to CF pathophysiology such as mucin secretion, mucin gene expression and cell proliferation are also mediated by PIP3 -induced translocation of PKC epsilon. If so, then PKC epsilon activation may mediate many of the pathological consequences of inflammation in CF and perhaps other degenerative lung conditions such as asthma, chronic obstructive pulmonary disorder and idiopathic pulmonary fibrosis. PROPOSED COMMERCIAL APPLICATION: Agents that reverse the translocation of PKC epsilon could be useful in the treatment of cystic fibrosis and other inflammatory diseases of the airways.